Small airway function, exhaled NO and airway hyper-responsiveness in paediatric asthma

Background: Asthma is a chronic inflammatory airway disorder known to involve the peripheral airways. Current guidelines state that diagnosis and treatment should be guided by symptoms and spirometry. FEV(1) is, however, a poor marker of small airway function and correlates poorly with asthma control and airway inflammation.

Aims: To assess the contribution of small airway dysfunction and inflammation in paediatric asthma. A secondary aim was to study the associations between small airway dysfunction, airway inflammation and airway hyper-responsiveness (AHR).

Methods: Small airway function was measured as LCI, S(cond) and S(acin), evaluated with the SF(6) multiple breath inert gas washout (MBW) technique, in 47 asthmatic children and 74 healthy controls. Exhaled NO at multiple exhalation flow rates including 50 mL/s (FENO(50)) was assessed to calculate alveolar NO and bronchial NO flux (a surrogate for airway inflammation). AHR was evaluated with isocapnoic dry air hyperventilation challenge in the asthmatic children.

Results: S(cond) was elevated in 31 (66%) and S(acin) in 18 (38%) of the asthmatic subjects. LCI was increased and FEV(1) decreased in 7 (15%) of the subjects with asthma. Individuals with AHR had higher S(cond) (p = 0.001) and FENO(50) (p < 0.0001) than those without AHR. The levels of FENO(50) and bronchial NO flux were elevated in asthmatic subjects compared with healthy controls. In asthma, S(cond) correlated with FENO(50) (r(s) = 0.42, p = 0.003) and alveolar NO (r(s) = 0.40, p = 0.011), and S(acin) correlated with alveolar NO (r(s) = 0.40, p = 0.015).

Conclusion: Dysfunction of small conducting airways is associated with airway inflammation and hyper-responsiveness in paediatric asthma.